Cell signaling by vasoactive agents

The vasoactive agents serotonin, endothelin-1, and angiotensin-2 have all been shown to produce proliferation of smooth muscle cells and thereby act as cellular mitogens. Although these vasoactive substances differ substantially in structure, their effects on cell signaling pathways are very similar. In general, following cellular ligation of the agents, reactive oxygen species (ROS) are generated through stimulation of NAD(P)H oxidase, and MAP kinases are subsequently activated. This leads to activation of multiple transcription factors, including AP-1, Egr-1, and GATA. Cell-cycling proteins are expressed to initiate the cell-growth response. Similar cellular responses by these vasoactive substances may be important in the production and release of cytokines, such as interleukin-6, which participate in vascular inflammation. The inflammatory responses of vasoactive substances are in need of further study.